scholarly journals Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF-κB signaling pathway

2017 ◽  
Vol 11 (5) ◽  
pp. 457-463 ◽  
Author(s):  
Yiming Xu ◽  
Ling Liu
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Signaling Pathway ◽  
Lung Inflammation ◽  
Macrophage Activation ◽  
Influenza Virus Infection

scholarly journals The Flavonoid Isoliquiritigenin Reduces Lung Inflammation and Mouse Morbidity during Influenza Virus Infection

2015 ◽  
Vol 59 (10) ◽  
pp. 6317-6327 ◽  
Author(s):  
Hussein Traboulsi ◽  
Alexandre Cloutier ◽  
Kumaraswamy Boyapelly ◽  
Marc-André Bonin ◽  
Éric Marsault ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Inflammatory Response ◽  
Lung Inflammation ◽  
Inflammatory Cell ◽  
Influenza Virus Infection ◽  
Cytokine Gene Expression ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment ◽  
Anti Inflammatory

ABSTRACTThe host response to influenza virus infection is characterized by an acute lung inflammatory response in which intense inflammatory cell recruitment, hypercytokinemia, and a high level of oxidative stress are present. The sum of these events contributes to the virus-induced lung damage that leads to high a level of morbidity and mortality in susceptible infected patients. In this context, we identified compounds that can simultaneously reduce the excessive inflammatory response and the viral replication as a strategy to treat influenza virus infection. We investigated the anti-inflammatory and antiviral potential activities of isoliquiritigenin (ILG). Interestingly, we demonstrated that ILG is a potent inhibitor of influenza virus replication in human bronchial epithelial cells (50% effective concentration [EC50] = 24.7 μM). In addition, our results showed that this molecule inhibits the expression of inflammatory cytokines induced after the infection of cells with influenza virus. We demonstrated that the anti-inflammatory activity of ILG in the context of influenza virus infection is dependent on the activation of the peroxisome proliferator-activated receptor gamma pathway. Interestingly, ILG phosphate (ILG-p)-treated mice displayed decreased lung inflammation as depicted by reduced cytokine gene expression and inflammatory cell recruitment. We also demonstrated that influenza virus-specific CD8+effector T cell recruitment was reduced up to 60% in the lungs of mice treated with ILG-p (10 mg/kg) compared to that in saline-treated mice. Finally, we showed that administration of ILG-p reduced lung viral titers and morbidity of mice infected with the PR8/H1N1 virus.

scholarly journals Metabolic pathways of lung inflammation revealed by high-resolution metabolomics (HRM) of H1N1 influenza virus infection in mice

2016 ◽  
Vol 311 (5) ◽  
pp. R906-R916 ◽  
Author(s):  
Joshua D. Chandler ◽  
Xin Hu ◽  
Eun-Ju Ko ◽  
Soojin Park ◽  
Young-Tae Lee ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Inflammatory Cytokines ◽  
Metabolic Pathways ◽  
Lung Inflammation ◽  
Influenza Virus Infection ◽  
H1n1 Influenza ◽  
H1n1 Influenza Virus ◽  
Tnf Α ◽  
Ifn Γ

Influenza is a significant health concern worldwide. Viral infection induces local and systemic activation of the immune system causing attendant changes in metabolism. High-resolution metabolomics (HRM) uses advanced mass spectrometry and computational methods to measure thousands of metabolites inclusive of most metabolic pathways. We used HRM to identify metabolic pathways and clusters of association related to inflammatory cytokines in lungs of mice with H1N1 influenza virus infection. Infected mice showed progressive weight loss, decreased lung function, and severe lung inflammation with elevated cytokines [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ] and increased oxidative stress via cysteine oxidation. HRM showed prominent effects of influenza virus infection on tryptophan and other amino acids, and widespread effects on pathways including purines, pyrimidines, fatty acids, and glycerophospholipids. A metabolome-wide association study (MWAS) of the aforementioned inflammatory cytokines was used to determine the relationship of metabolic responses to inflammation during infection. This cytokine-MWAS (cMWAS) showed that metabolic associations consisted of distinct and shared clusters of 396 metabolites highly correlated with inflammatory cytokines. Strong negative associations of selected glycosphingolipid, linoleate, and tryptophan metabolites with IFN-γ contrasted strong positive associations of glycosphingolipid and bile acid metabolites with IL-1β, TNF-α, and IL-10. Anti-inflammatory cytokine IL-10 had strong positive associations with vitamin D, purine, and vitamin E metabolism. The detailed metabolic interactions with cytokines indicate that targeted metabolic interventions may be useful during life-threatening crises related to severe acute infection and inflammation.

scholarly journals Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10

2009 ◽  
Vol 15 (3) ◽  
pp. 277-284 ◽  
Author(s):  
Jie Sun ◽  
Rajat Madan ◽  
Christopher L Karp ◽  
Thomas J Braciale
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Virus Infection ◽  
Lung Inflammation ◽  
Influenza Virus Infection ◽  
Effector T Cells

scholarly journals Influenza A Virus Infection Triggers Pyroptosis and Apoptosis of Respiratory Epithelial Cells through the Type I Interferon Signaling Pathway in a Mutually Exclusive Manner

2018 ◽  
Vol 92 (14) ◽  
Author(s):  
SangJoon Lee ◽  
Mikako Hirohama ◽  
Masayuki Noguchi ◽  
Kyosuke Nagata ◽  
Atsushi Kawaguchi
Keyword(s):  
Cell Death ◽  
Influenza Virus ◽  
Epithelial Cells ◽  
Virus Infection ◽  
Signaling Pathway ◽  
Influenza Virus Infection ◽  
Type I ◽  
Respiratory Epithelial Cells ◽  
Respiratory Epithelial ◽  
Early Phases

ABSTRACT Respiratory epithelial cell death by influenza virus infection is responsible for the induction of inflammatory responses, but the exact cell death mechanism is not understood. Here we showed that influenza virus infection induces apoptosis and pyroptosis in normal or precancerous human bronchial epithelial cells. Apoptosis was induced only in malignant tumor cells infected with influenza virus. In human precancerous respiratory epithelial cells (PL16T), the number of apoptotic cells increased at early phases of infection, but pyroptotic cells were observed at late phases of infection. These findings suggest that apoptosis is induced at early phases of infection but the cell death pathway is shifted to pyroptosis at late phases of infection. We also found that the type I interferon (IFN)-mediated JAK-STAT signaling pathway promotes the switch from apoptosis to pyroptosis by inhibiting apoptosis possibly through the induced expression of the Bcl-xL anti-apoptotic gene. Further, the inhibition of JAK-STAT signaling repressed pyroptosis but enhanced apoptosis in infected PL16T cells. Collectively, we propose that type I IFN signaling pathway triggers pyroptosis but not apoptosis in the respiratory epithelial cells in a mutually exclusive manner to initiate proinflammatory responses against influenza virus infection. IMPORTANCE Respiratory epithelium functions as a sensor of infectious agents to initiate inflammatory responses along with cell death. However, the exact cell death mechanism responsible for inflammatory responses by influenza virus infection is still unclear. We showed that influenza virus infection induced apoptosis and pyroptosis in normal or precancerous human bronchial epithelial cells. Apoptosis was induced at early phases of infection, but the cell death pathway was shifted to pyroptosis at late phases of infection under the regulation of type I IFN signaling to promote proinflammatory cytokine production. Taken together, our results indicate that the type I IFN signaling pathway plays an important role to induce pyroptosis but represses apoptosis in the respiratory epithelial cells to initiate proinflammatory responses against influenza virus infection.

scholarly journals Modelling within-host macrophage dynamics in influenza virus infection

2020 ◽  
Author(s):  
Ke Li ◽  
James M. McCaw ◽  
Pengxing Cao
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Viral Infection ◽  
Dynamic Model ◽  
Macrophage Activation ◽  
Negative Relationship ◽  
Influenza Virus Infection ◽  
Health Concern ◽  
Viral Shedding ◽  
Excessive Accumulation

AbstractHuman respiratory disease associated with influenza virus infection is of significant public health concern. Macrophages, as part of the front line of host innate cellular defence, have been shown to play an important role in controlling viral replication. However, fatal outcomes of infection, as evidenced in patients infected with highly pathogenic viral strains, are often associated with prompt activation and excessive accumulation of macrophages. Activated macrophages can produce a large amount of pro-inflammatory cytokines, which leads to severe symptoms and at times death. However, the mechanism for rapid activation and excessive accumulation of macrophages during infection remains unclear. It has been suggested that the phenomena may arise from complex interactions between macrophages and influenza virus. In this work, we develop a novel mathematical model to study the relationship between the level of macrophage activation and the level of viral shedding in influenza virus infection. Our model combines a dynamic model of viral infection, a dynamic model of macrophages and the essential interactions between the virus and macrophages. Our model predicts that the level of macrophage activation can be negatively correlated with the level of viral shedding when viral infectivity is sufficiently high. We further identify that temporary depletion of resting macrophages in response to viral infection is a major driver in our model for the negative relationship between macrophage activation and viral shedding, providing new insight into the mechanisms that regulate macrophage activation. Our model serves as a framework to study the complex dynamics of virus-macrophage interactions and provides a mechanistic explanation for existing experimental observations, contributing to an enhanced understanding of the role of macrophages in influenza viral infection.

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